1. Field of the Invention
The present invention relates generally to medical devices and methods. More particularly, the present invention relates to improved devices and methods for removing cerebrospinal fluid (CSF) from the CSF space of a patient to treat Alzheimer's disease and other diseases.
Alzheimer's disease is a degenerative brain disorder which is characterized clinically by progressive loss of memory, cognition, reasoning, judgment, and emotional stability and which gradually leads to profound mental deterioration and ultimately death. Alzheimer disease is the most common cause of progressive mental failure (dementia) in aged humans and is estimated to represent the fourth most common medical cause of death in the United States. Alzheimer's disease has been observed in all races and ethnic groups worldwide and presents a major current and future public health problem. The disease is currently estimated to affect about two to four million individuals in the United States alone and is presently considered to be incurable.
Recently, a promising treatment for Alzheimer's disease has been proposed. The proposed treatment relies on the removal of cerebrospinal fluid (CSF) from the CSF space (which includes the subarachnoid space, the ventricles, the vertebral column, and the brain interstitial space) of a patient suffering from Alzheimer's disease. The treatment is based on the principle that in at least some cases, the characteristic lesions, referred to as senile (or amyloid) plaque and other characteristic lesions in the brain associated with Alzheimer's disease result from the retention of certain toxic substances in the CSF of the patient. A number of suspected pathogenic substances, including toxic, neurotoxic, and pathogenic substances, have been identified to date, including 1-amyloid peptide (Aâ-42 amyloid), MAP, tau, and the like. It is believed that freshly produced CSF has lower levels or is free of these toxic substances. Thus, it is believed that removal of CSF from the patient's CSF space will reduce the concentration of such substances and significantly forestall the onset and/or progression of Alzheimer's disease. This treatment for Alzheimer's disease has recently been described in Rubenstein (1998) The Lancet, 351:283-285, and published PCT application WO 98/02202.
Hydrocephalus is another condition which is treated by removing CSF from a patient's CSF space, in particular from the cerebral ventricles. Hydrocephalus is characterized by an elevated intracranial pressure resulting from excessive production or retention of CSF, and the removal of such excess CSF has been found to be a highly effective treatment for the condition. Numerous specific catheters and shunts have been designed and produced for the treatment of hydrocephalus, occult hydrocephalus, and other CSF disorders.
The removal of CSF for the treatment of either Alzheimer's disease or hydrocephalus can be accomplished using a wide variety of apparatus which are capable of collecting CSF in the CSF space, preferably from the intracranial ventricles, and transporting the collected fluid to a location outside of the CSF space. Usually, the location will be an internal body location, such as the venous system or the peritoneal cavity, which is capable of harmlessly receiving the fluid and any toxic substances, but it is also possible to externally dispose of the CSF using a transcutaneous device. An exemplary system for removing CSF from a patient's CSF space is illustrated in FIG. 1 and includes an access component 12, a disposal component 14, and a flow control component 16.
While the system of FIG. 1 in general will be suitable for the treatment of both Alzheimer's disease and hydrocephalus, specific characteristics of the flow control component should be quite different because of the different nature of the two diseases. Treatment of hydrocephalus is best accomplished by controlling the flow rate of CSF from the CSF space to the disposal location in order to maintain intracranial pressure within normal physiological limits. Particularly suitable flow control characteristics for a flow control module in a hydrocephalus treatment system are illustrated in FIG. 2. FIG. 2 is taken from U.S. Pat. No. 4,781,672 which describes a flow control valve of the type used in the commercially available Orbis-Sigma® valve unit available from Nitinol Medical Technologies, Inc. Boston, Mass., 02210 (formerly from Cordis, Miami, Fla.). Briefly, the pressure P is the differential pressure between the CSF space and the disposal location. The patent teaches that the control valve establishes an initial flow rate Q1 of about 0.4 ml/min when the differential pressure P reaches an initial level P1 of 80 mm H2O and increases to a higher flow rate Q2 of 0.8 ml/min as the differential pressure increases to a higher value P2 of 350 mm H2O. When pressure P is below P1, there is essentially no flow. At pressures above P2, the flow is essentially unrestricted. Such valve flow characteristic are particularly suitable for treating hydrocephalus because for pressures below P1, there is no need to reduce pressure and thus no need to remove CSF. For pressures from P1 to P2, a controlled removal of CSF is desired to lower intracranial pressure with minimum risk of removing excessive amounts of CSF. When intracranial pressure exceeds P2 rapid removal of CSF is necessary to immediately lower intracranial pressure to a safer level. Such previous systems for draining CSF from the CSF space of the patient are generally not suitable for the treatment of patients suffering from Alzheimer's disease or other conditions relating to toxic substances in the CSF.
For these reasons, it would be desirable to provide devices and methods for removing CSF from the CSF space of a patient, where such devices and methods are particularly modified and optimized for treating Alzheimer's disease and other conditions relating to toxic substances in cerebrospinal fluid. Such devices and methods will preferably provide for the controlled removal of CSF from the patient in a manner which effectively removes the toxic substances to reduced levels without excessive removal of the CSF in a manner which places the patient at risk. Such objective will be met at least in part by the invention described hereinafter.
2. Description of Background Art
The treatment of Alzheimer's disease by removing cerebrospinal fluid from the CSF region of the brain is described in co-pending applications U.S. Ser. No. 08/678,191, filed on Jul. 11, 1996, and U.S. Ser. No. 08/901,023, filed on Jul. 25, 1997, both of which are assigned to the assignee of the present invention. The full disclosures of each of these two applications are incorporated herein by reference. The latter application is equivalent to WO 98/02202.
Methods and shunts for treating hydrocephalus are described in U.S. Pat. Nos. 3,889,687; 3,985,140; 3,913,587; 4,375,816; 4,377,169; 4,385,636; 4,432,853; 4,532,932; 4,540,400; 4,551,128; 4,557,721; 4,576,035; 4,595,390; 4,598,579; 4,601,721; 4,627,832; 4,631,051; 4,675,003; 4,676,772; 4,681,559; 4,705,499; 4,714,458; 4,714,459; 4,769,002; 4,776,838; 4,781,672; 4,787,886; 4,850,955; 4,861,331; 4,867,740; 4,931,039; 4,950,232; 5,039,511; 5,069,663; 5,336,166; 5,368,556; 5,385,541; 5,387,188; 5,437,627; 5,458,606; PCT Publication WO 96/28200; European Publication 421558; 798011; and 798012; French Publication 2 705 574; Swedish Publication 8801516; and SU 1297870. A comparison of the pressure-flow performance of a number of commercially available hydrocephalus shunt devices is presented in Czosnyka et al. (1998) Neurosurgery 42: 327-334. A shunt valve having a three-stage pressure response profile is sold under the Orbis-Sigma® tradename by Nitinol Medical Technologies, Inc. Boston, Mass. 02210 (formerly by Cordis). U.S. Pat. No. 5,334,315, describes treatment of various body fluids, including cerebrospinal fluids, to remove pathogenic substances therefrom.
Articles discussing pressures and other characteristics of CSF in the CSF space include Condon (1986) J. Comput. Assit. Tomogr. 10:784-792; Condon (1987) J. Comput. Assit. Tomogr. 11:203-207′; Chapman (1990) Neurosurgery 26:181-189; Magneas (1976) J Neurosurgery 44:698-705; Langfitt (1975) Neurosurgery 22:302-320.